This invention relates to the physiology of the heart, and more particularly, to non-alternating beat-to-beat fluctuations in T wave morphology.
The human heart is a four-chambered, muscular pump that contracts rhythmically due to the presence of cardiac muscle tissue. The heart is contained behind the sternum and within the cavity between the lower halves of the lungs. The heart lies within a double-walled sac called the pericardium, whose lower margin is anchored to the diaphragm. Thus, the heart is separated from the rest of the thoracic cavity, enclosed in a sac that serves as a protection against mechanical injury. The heart is divided into two distinct halves by a muscular wall called the septum. The right half receives blood that contains deoxygenated hemoglobin, while the left side receives blood containing oxygenated hemoglobin. Each side of the heart is divided into two chambers. Those at the top of the heart are called the atria and below them are the ventricles. The openings between the atria and the ventricles are guarded by atrioventricular valves, which prevent blood from passing back into a chamber.
Blood from throughout the body enters the right atrium through the superior and inferior venae cavae. Blood then flows into the right ventricle, and is pumped into the pulmonary artery and into the lungs, where contaminants (e.g., carbon dioxide) are removed and the blood is oxygenated. The oxygenated blood then flows back into the heart (i.e., the left atrium) via the pulmonary veins, flows into the left ventricle, and from there, is pumped into the aorta, which, via other arteries and capillaries, distributes the oxygenated blood throughout the body.
The invention describes novel non-alternating fluctuations in T wave morphology following chemical stress of an individual. These non-alternating fluctuations in T wave morphology are termed T wave lability. The invention provides for methods of detecting T wave lability in the cardiac electrical signals of an individual. The detection of T wave lability can be used in methods of the invention to detect or monitor abnormal cardiac activities in an individual, or to assess the risk of an individual for sudden death due to cardiovascular pathologies. The amount of T wave lability can be quantitated and used in methods provided by the invention to calculate a T wave lability index. The invention further provides a computer-readable storage medium for calculating a T wave lability index, as well as an apparatus for detecting T wave lability and for calculating a T wave lability index for an individual. The invention also provides an article of manufacture for chemically stressing an individual for the purpose of determining a T wave lability index.
In one aspect, the invention provides a method of detecting T wave lability in an individual. T wave lability is detected by obtaining signals representative of electrical activity of the heart of the individual and detecting any non-alternating beat-to-beat fluctuations in the morphology of the T wave. Such non-alternating beat-to-beat fluctuations in the T wave morphology are indicative of the individual having T wave lability.
In another aspect, the invention provides a method for detecting or monitoring abnormal cardiac activities in an individual, including obtaining signals representative of electrical activity of the heart and detecting the presence of non-alternating beat-to-beat fluctuations in T wave morphology. The presence of non-alternating beat-to-beat fluctuations in T wave morphology indicates abnormal cardiac activities in the individual.
In yet another aspect of the invention, there is provided a method of obtaining a T wave lability index, including obtaining signals representative of electrical activity of the heart of an individual, eliminating ectopic beats and the sinus beats preceding and following the ectopic beats, and calculating the maximal value of root-mean-square differences for isochronic points of the repolarization interval between pairs of consecutive beats. Generally, ectopic beats include a ventricular premature contraction or an atrial premature contraction. In certain embodiments, the signal can be filtered, baseline fluctuation can be removed, and/or the maximal value of root-mean-square differences can be normalized to the absolute magnitude of the signal-averaged QRS complex.
The invention also provides a method of identifying non-alternating beat-to-beat fluctuations in T wave morphology in cardiac electrical signals, and calculating a T wave lability index as a function of the non-alternating beat-to-beat fluctuations in T wave morphology.
In still yet another aspect of the invention, there is provided a method of assessing the risk of an individual for sudden death due to cardiovascular pathology. This method includes obtaining signals representative of electrical activity of the heart of the individual, detecting the presence of non-alternating beat-to-beat fluctuations in T wave morphology in the cardiac electrical signal, and determining a T wave lability index from the non-alternating beat-to-beat fluctuations in T wave morphology. A T wave lability index that is significantly different than a reference value indicates an increased risk of the individual for sudden death due to a cardiovascular disease. Individuals at risk for sudden death due to cardiovascular pathology may present with QT prolongation, QT variability, ectopy, TWA, OHCA, syncope, angina, late potentials, QT dispersion, wide complex tachycardia, unexplained seizures or unexplained near drownings. Representative examples of cardiovascular pathologies include long QT syndrome, hypertrophic cardiomyopathy, dilated cardiomyopathy, coronary artery disease, myocardial ischemia, idiopathic ventricular fibrillation and Brugada syndrome.
Generally, a chemical stressor is administered to an individual with regard to practicing the above-described methods. Representative chemical stressors include catecholamine compounds, such as dobutamine, epinephrine, phenylephrine and atropine. Typically, the amount of the chemical stressor is selected to achieve a heart rate within a desired range, for example, greater than 100 beats per minute (bpm).
In addition, the invention further provides a computer-readable storage medium having instructions stored thereon for causing a programmable processor to identify non-alternating beat-to-beat fluctuations in T wave morphology in signals representative of electrical activity of the heart of an individual and determine a T wave lability index as a function of the non-alternating beat-to-beat fluctuations in T wave morphology. As used herein, ectopic beats include ventricular premature contractions and atrial premature contractions. Typically, the processor determines a T wave lability index as a function of the non-alternating beat-to-beat fluctuations in T wave morphology by eliminating ectopic beats and the sinus beats preceding and following the ectopic beats and calculating the maximal value of root-mean-square differences for isochronic points of the repolarization interval between pairs of consecutive beats. The processor can also perform functions such as filtering the signal, removing baseline fluctuation and normalizing the maximal value of the root-mean-square differences to the absolute magnitude of the signal-averaged QRS complex.
The invention also provides an apparatus for determining a T wave lability index for an individual. The apparatus can include one or more transducers for obtaining signals representative of electrical activity of the heart of the individual and a processor for analyzing the electrical signals and determining the T wave lability index. By way of example, the transducers can be electrodes. In one embodiment, the apparatus generates a visual representation of the electrical signals. In another embodiment, the apparatus generates a signal indicative of the presence of ectopic beats. Generally, obtaining and analyzing the signals occurs concurrently.
The signals representative of electrical activity of a heart are oftentimes generated into an electrocardiogram. Electrical signals obtained from a precordial lead V4 are exemplified herein. In addition, the heart rate of the individual is usually monitored during a procedure to determine T wave lability and a T wave lability index.
In another aspect of the invention, there is provided an article of manufacture for chemically stressing an individual for the purpose of determining a T wave lability index for the individual. The article of manufacture (i.e., a kit) can include a vial comprising an appropriate dose of a catecholamine compound, at least one additional vial comprising a different dose of the same or a different catecholamine compound, and a label or package insert that indicates that the contents can be used in a procedure to determine a T wave lability index. Oftentimes, the doses are different concentrations of catecholamine compounds and each of the vials are preferably labeled with the respective dose.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the drawings and detailed description, and from the claims.